Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia: results of a double-blind, placebo-controlled, randomized clinical trial using two doses of the aromatase-inhibitor atamestane. Atamestane Study Group.

BACKGROUND: The concept of estrogen withdrawal by an aromatase inhibitor in the treatment of benign prostatic hyperplasia (BPH) was assessed in a prospective, randomized, double-blind, placebo-controlled multicenter trial. METHODS: Two hundred and ninety-two patients with clinical symptoms of BPH were randomly allocated to one of the following treatments for 48 weeks: placebo or the selective aromatase inhibitor, atamestane, at a daily dose of 100 mg or 300 mg. Both doses of atamestane significantly reduced serum concentrations of estradiol and estrone, and produced a slight, dose-dependent, counter-regulatory increase in peripheral androgen concentration. RESULTS: Clinical symptoms improved during treatment in all three groups. Even after 48 weeks, the effect of active treatment did not exceed the effect seen with placebo. Overall tolerance of 100 mg atamestane was excellent, but 300 mg showed a slightly increased incidence of side effects compared with placebo. CONCLUSIONS: The conclusion from this study is that the reduction in estrogen concentration using the selective aromatase inhibitor atamestane has no effect on clinically established BPH.

Circulating testosterone, prostatic nuclear androgen receptor and time to progression in patients with metastatic disease of the prostate treated by orchiectomy.

The content of nuclear androgen receptors (ARn) in prostatic carcinoma biopsies is not predictive for the duration of response of the tumor to endocrine therapy. Recently pre-treatment plasma testosterone has been suggested to be predictive in this respect. Therefore, pre-treatment plasma testosterone (T) and sex hormone binding globulin (SHBG) levels were studied in 31 patients aged 72 +/- 10 years (range: 45-87) with stage D2 carcinoma of the prostate treated by orchiectomy. In 26 of these patients, the ARn level of the carcinoma was also known (61 +/- 41 fmol/mg protein; range 0-169). Plasma T levels (mean: 13.7 +/- 6.1 nmol/l) varied widely (range: 2.4-25.4), as did plasma SHBG (32.5 +/- 19.3 nmol/l; range 4.4-78.8), and time to progression (TTP; 14.6 +/- 11.2 months; range 1-48). Plasma T was found to be correlated to age (Rs = 0.537; P less than 0.01) and TTP (Rs = 0.4495; P less than 0.02). Tissue ARn and plasma SHBG did not correlate to any of the parameters studied.

Hormone receptors in human prostate cancer.

The relative success with which the response of breast cancer to endocrine therapy can be predicted by assay of female sex steroid receptors has led to attempts to use measurement of androgen receptors in neoplastic prostate tissue for predicting the success of anti-androgen therapy in prostate cancer. Hitherto hopes have not been fulfilled. Androgen receptors are present in almost all prostate samples, but with inhomogeneous distribution. No relationship was found between androgen receptor levels in needle aspirate and prognosis in prostatic carcinoma. Receptors for oestrogen, progestin and prolactin were also studied for identification of possible prognostic indicators. Progestin receptors appear to be present in prostatic tissue. Lack of consensus regarding prostatic oestrogen and prolactin receptors is due partly to their low (if any) concentrations and partly to differing methodology and interpretation of results. Oestrogen, progestin and prolactin receptors seem to lack prognostic significance in prostatic cancer. These findings and the high initial response rate of prostatic carcinoma to endocrine therapy indicate that further studies should focus on elucidating how such tumours become hormone-independent.

Early orchiectomy for patients with stage D1 prostatic carcinoma.

Staging lymphadenectomy revealed stage D1 disease in 30 of 94 patients with clinically localized prostatic carcinoma. Early orchiectomy resulted in a 46 per cent treatment failure rate after 45 months and established local disease control in almost all patients. The interval to treatment failure in this group compares favorably to the progression rate in patients treated with other modalities.

Nuclear androgen receptor content in biopsy specimens from histologically normal, hyperplastic, and cancerous human prostatic tissue.

Androgen receptors (ARn) were assayed in nuclear extracts of prostatic biopsies from 60 patients with benign prostatic hyperplasia (BPH) and 82 patients with prostatic cancer (PC), with an exchange assay using heparin extraction, labelling with 3H-R1881, and protamine sulphate precipitation. The content of ARn of BPH biopsies (38 +/- 34 fmol/mg protein [mean +/- SD]; n = 70) was not different from that of PC biopsies (39 +/- 32 fmol/mg protein; n = 115). Biopsies showing essentially normal prostatic tissue had a lower ARn content (12 +/- 13 fmol/mg protein; n = 6). The content of ARn was independent of the age of the patient and of the histological grade of the carcinomas. A considerable variation in ARn content within tumors of individual patients was found, indicating that ARn are not uniformly distributed over prostatic tissue; ie, cells with high and low receptor content may coexist in different proportions in different regions of the prostate. Therefore, assays on multiple biopsies may be required for a proper estimation of the mean receptor content. The question remains, however, whether the behavior of the tumor is adequately predicted by the mean receptor level or, for instance, by the region with the lowest receptor content.